Collaboration between the University of Michigan Taubman Health Sciences library and the University of Michigan Medical School Office of Research.

Librarians have traditionally facilitated research development resulting in grants through performing biomedical literature searches for researchers. The librarians at the Taubman Health Sciences Library of the University of Michigan have taken additional steps forward by instituting a proactive approach to assisting investigators. To accomplish this, the librarians have taken part in a collaborative effort with the University of Michigan Medical School Office of Research. Through this partnership, both units have created and adopted various techniques intended to facilitate the submission of grants, thus allowing researchers more time to conduct their primary activities.

The biochemical basis of life history adaptation: molecular and enzymological causes of NADP(+)-isocitrate dehydrogenase activity differences between morphs of Gryllus firmus that differ in lipid biosynthesis and life history.

Although whole-organism aspects of life-history physiology are well studied and molecular information (e.g., transcript abundance) on life-history variation is accumulating rapidly, much less information is available on the biochemical (enzymological) basis of life-history adaptation. The present study investigated the biochemical and molecular causes of specific activity differences of the lipogenic enzyme, NADP(+)-isocitrate dehydrogenase, between genetic lines of the wing-polymorphic cricket, Gryllus firmus, which differ in lipid biosynthesis and life history. With one exception, variation among 21 Nadp(+)-Idh genomic sequences, which spanned the entire coding sequence of the gene, was restricted to a few synonymous substitutions within and among replicate flight-capable or flightless lines. No NADP(+)-IDH electromorph variation was observed among individuals within or among lines as determined by polyacrylamide gel electrophoresis. Nor did any NADP(+)-IDH kinetic or stability parameter, such as K(M) for substrate or cofactor, k(cat), or thermal denaturation, differ between flight-capable and flightless lines. By contrast, line differences in NADP(+)-IDH-specific activity strongly covaried with transcript abundance and enzyme protein concentration. These results demonstrate that NADP(+)-IDH-specific activity differences between artificially selected lines of G. firmus are due primarily, if not exclusively, to genetic variation in regulators of NADP(+)-IDH gene expression, with no observed contribution from altered catalytic efficiency of the enzyme due to changes in amino acid sequence or posttranslational modification. Kinetic analyses indicate that in vitro differences in enzyme-specific activity between flight-capable and flightless lines likely occur in vivo. This study constitutes the most comprehensive analysis to date of the biochemical and molecular causes of naturally occurring genetic variation in enzyme activity that covaries strongly with life history.

Sexual health problems of adolescents attending a sexual health service.

OBJECTIVE: To determine whether adolescents who present at a sexual health service aged 13 have more sexual health problems in later years than those who present aged 15. METHODS: A case-note review was done in 2009 to identify sexual health problems for all 13-year-olds who registered with Sandyford sexual health service from April 2003 until December 2004 (group 1). This was compared with selected notes from adolescents who were 15 years old at the time of registration (group 2). RESULTS: Eighty-eight youths aged 13 and 632 aged 15 registered in the aforementioned period. Ninety records of 15-year-olds were selected for comparison. Twenty two of the 86 girls in group 1 and 31 of the 87 girls in group 2 had at least one pregnancy. Twenty-one adolescents in group 1 and 25 of those in group 2 had a sexually transmitted infection. Thirteen youths in group 1 and one in group 2 had suffered a sexual assault. CONCLUSION: Adolescents aged 13 at first registration with this service have more sexual health problems and warrant additional support throughout their teenage years. A very young age at first registration should prompt health professionals to provide additional clinical, emotional and social support.

Purification and characterization of cytoplasmic NADP+-isocitrate dehydrogenase, and amplification of the NADP+-IDH gene from the wing-dimorphic sand field cricket, Gryllus firmus.

Cytoplasmic NADP(+)-isocitrate dehydrogenase (NADP(+)-IDH) has been purified and characterized, and its gene sequenced in many animal, plant, and yeast species. However, much less information is available on this enzyme-gene in insects. As a first step in investigating the biochemical and molecular mechanisms by which NADP(+)-IDH contributes to adaptations for flight vs. reproduction in insects, the enzyme was purified to homogeneity in the wing-dimorphic cricket, Gryllus firmus, characterized, and its corresponding gene sequenced. Using a combination of polyethylene glycol precipitation, Cibacron-Blue affinity chromatography, and hydrophobic interaction chromatography the enzyme was purified 291-fold (7% yield; specific activity = 15.8 µmol NADPH/min/mg protein). The purified enzyme exhibited a single band on SDS PAGE (46.3 kD), but consisted of two N-terminal amino acid sequences that differed in the first two amino acids. Purified enzyme exhibited standard Michaelis-Menten kinetics at pH 8.0 and 28° C (K(M(NADP+)) = 2.3 ± 0.4 µM; K(M(Na+-Isocitrate)) = 14.7 + 1.8 µM). Subunit molecular mass and K(M)S were similar to published values for NADP(+)-IDHs from a variety of vertebrate and two insect species. PCR amplification of an internal sequence using genomic DNA followed by 3' and 5' RACE yielded a nucleotide sequence of the mature protein and translated amino-acid sequences that exhibited high similarity (40-50% and 70-80%, respectively) to sequences from insect and vertebrate NADP(+)-IDHs. Two potential ATG start codons were identified. Both Nterminal amino-acid sequences matched the nucleotide sequence, consistent with both enzyme forms being transcribed from the same gene, although these variants could also be encoded by different genes. Bioinformatic analyses and differential centrifugation indicated that the majority, if not all, of the enzyme is cytoplasmic. The enzyme exhibited high specific activity in fat body, head and gut, and a single band on native PAGE.

Current Practices Among Speech-Language Pathologists for Mild Traumatic Brain Injury: A Mixed-Methods Modified Delphi Approach.

Purpose The study purpose was to capture the clinical practice patterns of speech-language pathologists (SLPs) treating mild traumatic brain injury (mTBI; concussion). Study aims were to (a) characterize expert SLP practice patterns for the management of mTBI and (b) use qualitative content analysis to explore areas of quantitative variability within participants' responses. Method Using a modified Delphi approach, SLPs completed an online survey, with Round 1 responses shaping questions for Round 2. Round 2 results were analyzed using a concurrent partially mixed-methods approach with quantitative and qualitative items. Quantitative consensus agreement levels were set prestudy at 75% agreement or higher. Topic-level items that did not reach consensus were analyzed using qualitative content analysis. Participants SLPs engaging in a specialty mTBI-SLP networking group were invited to participate. Round 1 had nine participants (United States: 4, Canada: 5). Round 2 had 18 participants (United States: 12, Canada: 6), with a mean of 15.7 years of experience in mTBI (range: 3-33) and a mean of 7.6 clients with mTBI seen weekly (range: 1-25). Results Nearly all topic-level practice items met quantitative consensus (42/45). Consensus areas included using conceptual frameworks, interprofessional teaming, assessment and intervention practices, goal setting, and outcomes. Functional, collaborative, and client-centered care anchored clinical practice. Areas lacking consensus included SLP roles in mTBI mental and somatic health symptoms, specific measurement tools, and intervention dosages. Qualitative themes that emerged included limited interprofessional awareness for the role of SLPs in mTBI and challenges in measurement selection. Conclusions Study aims were met with clear consensus on clinical patterns implemented by SLPs specializing in mTBI. Results will inform both current clinical practices and future practice guidelines. High-level guidance and advocacy are needed to clarify SLP practice concerns and advance interprofessional education. Future work should address identified gaps, including targeted assessment tools and consensus on intervention methods.

Purification and characterization of 6-phosphogluconate dehydrogenase from the wing-polymorphic cricket, Gryllus firmus, and assessment of causes of morph-differences in enzyme activity.

Considerable information exists on the physiological correlates of life history adaptation, while molecular data on this topic are rapidly accumulating. However, much less is known about the enzymological basis of life history adaptation in outbred populations. In the present study, we compared developmental profiles of fat body specific activity, kinetic constants of homogeneously purified and unpurified enzyme, and fat body enzyme concentration of the pentose-shunt enzyme, 6-phosphogluconate dehydrogenase (6PGDH, E.C.1.1.1.44) between the dispersing [long-winged, LW(f)] and flightless [short-winged, SW] genotypes of the cricket Gryllus firmus. Neither kcat nor the Michaelis constant for 6-phosphogluconate differed between 6PGDH from LW(f) versus SW morphs for either homogeneously purified or unpurified enzyme. Purified enzyme from the LW(f) morph exhibited reduced KM for NADP(+), but this was not observed for multiple KM(NADP+) estimates for unpurified enzyme. A polyclonal antibody was generated against 6PGDH which was used to develop a chemiluminescence assay to quantify 6PGDH concentration in fat body homogenates. Elevated enzyme concentration accounted for all of the elevated 6PGDH specific activity in the LW(f) morph during the juvenile and adult stages. Finally, activity of another pentose-shunt enzyme, glucose-6-phosphate dehydrogenase, strongly covaried with 6PGDH activity suggesting that variation in 6PGDH activity gives rise to variation in pentose shunt flux. This is one of the first life-history studies and one of the few studies of intraspecific enzyme adaptation to identify the relative importance of evolutionary change in enzyme concentration vs. kinetic constants to adaptive variation in enzyme activity in an outbred population.

Teenagers' use of tobacco and their perceptions of tobacco control initiatives.

BACKGROUND: Tobacco use leads to more deaths each year than any other single factor. This research examined teenagers' perceptions of anti-tobacco messages to determine which campaigns and educational approaches were most effective in preventing tobacco use among youth. METHODS: Students from five rural high schools in western Pennsylvania were included in this survey-based study (N = 204). RESULTS: A total of 30% of the study population reported current tobacco use. Tobacco users held more negative perceptions of anti-tobacco messages than non-users. A majority of students held supportive views about anti-tobacco education programs that were facilitated by peer leaders. CONCLUSIONS: Existing anti-tobacco campaigns and education are essential components of tobacco control initiatives. Students' perspectives provide novel insights that educators and campaign designers should consider as they develop anti-tobacco programs.

What do clients of a young people's sexual health service recall about their sex education programme at school?

OBJECTIVES: To assess young people's recall of school-based sexual health education. METHODS: Clients attending The Place, an open-access sexual health service for young people, were asked to recall whether they had received teaching on key areas of sex education outlined in the Scottish Executive's draft Sexual Health and Relationship Strategy and Greater Glasgow NHS Board's guidelines for sex education in schools.Their responses were analyzed by age, sex, and type of school attended. RESULTS: Although most could remember receiving some teaching about risks of sexual activity, there was little recall of teaching in positive areas of sexual health, such as having good relationships, rights and responsibilities, and being good parents. CONCLUSIONS: Further research is needed to establish why recall of taught sex education is low in this group of clients, and how to improve retention of important sexual education information.

Stereoselective and improved syntheses and anticancer testing of 3'-O-silatranylthymidines.

A stereoselective synthesis of 3'-O-((R,R,R)-trimethylsilatranyl)thymidine (R,R,R-1) and synthesis of 3'-O-silatranylthymidine (5) via an improved silatranylation procedure using tetrakis(dimethylamino)silane are reported. Diastereomeric mixture 1 showed more activity than R,R,R-1 or 5 in a primary anticancer screen against breast, CNS, and lung cell lines; demonstrating the import of the configuration and presence, respectively, of the silatrane methyl groups for growth inhibition.